Abstract B24: De-clotting tumor to improve the perfusion, distribution and efficacy of chemotherapy and nanotherapeutics

Tumors exhibit several physical and physiological barriers that limit the distribution of molecules as small as oxygen; tumor barriers are compressed vessels due to solid stress, immature vasculature with geometric resistances, high interstitial fluid pressure, and the dense extracellular matrix. Tumors are also thrombotic in nature; pancreatic, colon, gastric, lung, ovarian cancers, melanoma, glioblastoma, lymphomas, etc. are associated with a high rate of thrombosis. Solid tumors obstruct venous return which cause static blood flow, endothelial cell injury, and coagulation activation. We hypothesize that coagulation/thrombosis act as a drug transport barrier inside the tumors and the use of anticoagulants or anti-thrombotics overcome this barrier. We posit that perfusion and penetration of drugs trap in thrombotic tumor vessels, whereas the small intra-thrombotic spacing within the vessel wall and interstitial space of tumor retards the movement of particles. In this work, we show that heparin or heparin-based anticoagulants prevent clot formation in tumors, enhances blood perfusion and nanoparticle distribution, and potentiates both chemo- and nano-therapeutic efficiency in tumor treatment.We compared the vessel perfusion and their thrombi fractions in tumors of P-selectin-/- vs wild-type (WT) mice. B16f10 melanoma cells were grown subcutaneously in P-selectin-/- and WT mice and Cy7 labeled dextran (Dex-Cy7; as a marker of perfused vessels) and Cy5.5 labeled fibrinoigen (F...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Microfluidics and Model Systems Source Type: research